PXD043082

PXD043082 is an original dataset announced via ProteomeXchange.

Title	ULK phosphorylation of STX17 controls autophagosome maturation via FLNA
Description	Autophagy is a conserved and tightly regulated intracellular quality control pathway. ULK is a key kinase in autophagy initiation, but whether ULK kinase activity also participates in late stages of autophagy remains unknown. Here, we found that the autophagosomal SNARE protein, STX17, is phosphorylated by ULK at residue S289, beyond which it localizes specifically to autophagosomes. Inhibition of STX17 phosphorylation prevents such autophagosome localization. FLNA was then identified as a linker between ATG8 family proteins (ATG8s) and STX17 with essential involvement in STX17 recruitment to autophagosomes. Phosphorylation of STX17 S289 promotes its interaction with FLNA, activating its recruitment to autophagosomes and facilitates autophagosome-lysosome fusion. Disease causative mutations around the ATG8s- and STX17-binding regions of FLNA disrupt its interactions with ATG8s and STX17, inhibiting STX17 recruitment and autophagosome-lysosome fusion. Cumulatively, our study reveals an unexpected role of ULK in autophagosome maturation, uncovers its regulatory mechanism in STX17 recruitment, and highlights a potential association between autophagy and FLNA.
HostingRepository	iProX
AnnounceDate	2023-06-18
AnnouncementXML	Submission_2024-02-22_02:16:29.576.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Shuaixin Gao
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-18 19:59:51	ID requested
1	2023-06-18 20:00:17	announced
⏵ 2	2024-02-22 02:16:30	announced	2024-02-22: Update information.

Wang Y, Que H, Li C, Wu Z, Jian F, Zhao Y, Tang H, Chen Y, Gao S, Wong CCL, Li Y, Zhao C, Rong Y, ULK phosphorylation of STX17 controls autophagosome maturation via FLNA. J Cell Biol, 222(8):(2023) [pubmed]

submitter keyword: ULK phosphorylation, STX17, autophagosome, FLNA

Yueguang Rong
contact affiliation	Cell Architecture Research Center, Huazhong University of Science and Technology
contact email	rongyueguang@hust.edu.cn
lab head
Shuaixin Gao
contact affiliation	Center for Precision Medicine Multi-Omics Research, Peking University Health Science Center, Peking University
contact email	gaoshuaixin@126.com
dataset submitter

iProX dataset URI